Dissertation > Biological Sciences > Anthropology > Human Genetics

Gene Mapping and Mutation Detection of A CIN with Hearing Impairment Family

Author CuiXiaoZuo
Tutor LiuJingYu
School Huazhong University of Science and Technology
Course Biochemistry and Molecular Biology
Keywords CIN with hearing impairment Linkage analysis Mutation detection FRMD7 Restriction fragment length polymophis
CLC Q987
Type Master's thesis
Year 2009
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Congenital idiopathic nystagmus is a common ocular motor disorder. It may be present at birth within the first 6 months of life. Nystagmus is mainly characterized by involuntary periodic and rapid to and fro oscillations of the eyes. Eye movement may present as several forms, horizontal, vertical, pendular and the mixed forms. The nystagmus intensity may decrease on convergence or with voluntary eyelid closure, or in the dark place; and may disappear when the patient falls asleep, and it has exceptions too. In some circumstance, it is associated with abnormal head posture. The etiology of congenital nystagmus is not clear, and is likely to be due to abnormal development of areas in the brain controlling eye movements and gaze stability. Congenital nystagmus is usually accompanied by strabismus, amblyopia or myopia. The nystagmus is highly variable between patients, and is often subsides with age. Between 7% and 30% of CN patients have a positive family history. Autosomal dominant, autosomal recessive, and X-linked patterns of inheritance have been described. It has been suggested that X-linked inheritance is the most common form, the different inheritance patterns cannot be distinguished phenotypically. So far, at least 6 loci for nystagmus have been identified on Xq26-q27(NYS1), 6p12(NYS2), 7p11(NYS3), 13q31-q33(NYS4), 18q22.3-q23 and Xp11.4-p11.3. Only one gene FRMD7(FERM domain containing protein 7) has been identified in 2006.In this study, a large five-generation Chinese family from Jilin Provience with X-linked recessive congenital nystagmus, head turn and sensori-neural hearing impairment have identified and characterized. Linkage was identified with marker DXS1047. Haplotype analysis defined the causative gene between DXS1001 and DXS1227. The FRMD7 gene is closely linked to the disease of this family. Mutational analysis of all exons and exon-intron boundaries of FRMD7 was carried out using direct DNA sequence analysis. A novel insertion mutation c.998999 insA of the FRMD7 is found in proband. All male patients in the family were hemizygous for the mutation; the female carriers were heterozygous for the mutation. To confirm that c.998999 insA mutation is associated with the disease in the family, RLFP analysis was carried out. The c.998999 insA mutation was not identified in 25 normal females or 50 normal males. These results showed that the insertion mutation c.998999 insA is a cause of this disease in the large Chinese family. These results expand the mutation spectrum of clinical phenotypes associated with FRMD7 mutations. The cuasing head turn and progressive sensori-neural hearing impairment mechanism beside nystagmus of mutation c.998999 insA of FRMD7 was discussed.

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